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1/19. Peripheral T-cell lymphoma of AILD (angioimmunoblastic lymphadenopathy with dysproteinemia) type involving gastrointestinal tract. A morphologic, phenotypic and genotypic study.

    A case of angioimmunoblastic lymphadenopathy with dysproteinemia (AILD) which showed widespread involvement of the gastrointestinal tract is reported. A lymph node biopsy specimen showed the characteristic histological features of AILD. During the progression of the illness, lymphomatous lesions developed in the gastrointestinal tract, complicated by cytomegalovirus infection. A double immunoenzymatic study using a combination of Ki-67 antibody and antibodies against surface antigens demonstrated that CD3 , CD4 , and/or T-cell receptor (TCR) beta cells were predominant (67-68%) among the population of proliferating Ki-67% cells, rather than CD8 or CD22 cells. Clonal rearrangement of the TCR beta chain gene was also detected. These findings provide further evidence for the neoplastic nature of lesions of this type, and the diagnosis of peripheral T-cell lymphoma.
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2/19. Treatment of a patient with a nodal peripheral T-cell lymphoma (angioimmunoblastic T-Cell lymphoma) with a human monoclonal antibody against the CD4 antigen (HuMax-CD4).

    A patient with a CD4 refractory peripheral T-cell lymphoma (PTL), subtype angioimmunoblastic T-cell lymphoma (AILD), was treated with a human monoclonal anti-CD4 antibody (HuMax-CD4) iv once weekly for 10 wk. Early during treatment all palpable enlarged lymph nodes disappeared. A decline of normal CD4 T-cells in the blood mirrored the treatment effect. Shortly after stopping treatment the patient relapsed with new enlarged lymph nodes. This time no antitumor effect was seen when HuMax-CD4 treatment was reinstituted. No severe side effects were observed during the antibody treatment. This case report is the first describing that HuMax-CD4 has antilymphoma activity in PTL and is an interesting drug to study further in patients with CD4 PTL.
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3/19. Multicentric angiofollicular lymph node hyperplasia with peripheral neuropathy, pseudotumor cerebri, IgA dysproteinemia, and thrombocytosis in women. A distinct syndrome.

    Four women with multicentric angiofollicular lymph node hyperplasia had a distinct clinical syndrome characterized by peripheral neuropathy, pseudotumor cerebri, IgA dysproteinemia, and thrombocytosis. The nodes displayed typical morphologic changes of the plasma cell variant of multicentric angiofollicular lymph node hyperplasia. The pathologic changes are morphologically distinct from angioimmunoblastic lymphadenopathy with dysproteinemia although clinical similarities do exist. In these four cases, the lymphadenopathy was usually bulky and multicentric. There was frequent splenic involvement. The neuropathies were severe and disabling. Clinical courses have been variable with some responses to therapy with steroids and alkylating agents. No neoplastic transformations have occurred. Multicentric angiofollicular lymph node hyperplasia may represent a reactive lesion in which the antigenic stimulus is unknown but results in follicular hyperplasia, angiogenesis, and the systemic manifestations of hyperimmune stimulation. We believe this clinical syndrome may represent a distinct variant of multicentric angiofollicular lymph node hyperplasia, and it requires close observation for neoplastic transformation and other complications of its multisystem nature.
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4/19. scabies-associated angioimmunoblastic lymphadenopathy.

    A systemic disorder characterized by fever and reactive lymphadenopathy developed in a patient with scabies infestation. Regression of all clinical symptoms and signs occurred after antiscabies therapy. Two months later, the whole clinical picture reappeared concomitantly with scabies reinfestation. Subsequent lymph node biopsy demonstrated typical angioimmunoblastic lymphadenopathy (AILD). It is plausible that persistent antigenic stimulation caused by scabies infection was of pathogenetic importance in the induction of the syndrome of AILD. Infectious agents should be considered and looked for in patients with AILD, since they may play a role in the evolution of this disease.
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5/19. Angioimmunoblastic lymphadenopathy with dysproteinemia. A pathogenetic link between lymphoid proliferation and malignant lymphoma.

    Two patients with angioimmunoblastic lymphadenopathy with dysproteinemia (AILD) were studied. Both patients had marked increases in all three major immunoglobulin classes, and both lacked suppressor cell activity in vitro. These findings are consistent with the theory that AILD is a defectively regulated immune response to an unidentified antigen(s) and could provide clues to the pathogenesis of other lymphoproliferative disorders as well.
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6/19. Angio-immunoblastic lymphadenopathy (AIL) or T-cell malignant lymphoma of AIL-type. A histopathological, immunohistochemical and ultrastructural study of 8 cases.

    Eight cases of AIL-type T-cell malignant lymphoma are reported. The clinical symptoms are the same as those described in AIL: fever, malaise, weight loss, skin rashes, polyadenopathy, and splenomegaly. However, some differences can be noted: the absence of hepatomegaly in all cases but one, the absence of polyclonal hypergammapathy in all cases but one, and predominance in females. The lymph node modifications comprise diffuse infiltrations of lymphoid cells with irregular nuclei and pale cytoplasm, associated with a large number of immunoblasts and plasma cells. Some eosinophilic granulocytes and epithelioid cells can be seen. hyperplasia of the vessels and remnants of follicles, sometimes with proliferation of follicular dendritic cells, are prominent features. The immunolabelling study demonstrates the presence of an important T-cell population all expressing a high predominance of CD 4 phenotype. These findings are in accordance with those published in europe and in contrast with those of some of the Japanese cases, particularly the first patients published by Shimoyama et al. The differential diagnosis with AIL is based on the presence of clusters of mainly large cells with a pale cytoplasm, on the loss of expression of one T cell marker, as in 3 cases of our series, and on the presence of a high percentage of lymphoid cells engaged in the mitotic cycle as demonstrated with the Ki 67 monoclonal antibody. However, to draw a clear cut difference between AIL-type T-cell lymphoma and AIL considered as a prelymphomatous dysimmune lymphadenopathy, only the demonstration of cytogenetic abnormalities, as in one of our cases or of rearrangement of the genes coding for beta and/or gamma chain of the antigen receptor of T-cell are valuable criteria. The follow-up of our series is not long enough to appreciate the prognosis. Three patients died, one from a glioma. All the other cases, treated with polychemotherapy show total remission with an evolution of 10 to 39 months.
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7/19. immunoblastic lymphadenopathy-like T-cell lymphoma with multiple cutaneous and visceral involvements.

    Morphologic and immunological findings found in a patient with immunoblastic lymphadenopathy (IBL)-like T-cell lymphoma (IBL-T) are presented. Though the initial clinical features were suggestive of IBL, multiple cutaneous and visceral tumors appeared later in his course. The cutaneous lesion is considered to be unique, because the neoplastic T cells with suppressor/cytotoxic (S/C) phenotype showed focal epidermotropism, resulting in necrosis and ulceration of the overlying epidermis. An interesting feature in IBL-T is the frequent association of polyclonal hypergammaglobulinemia, yet the neoplastic T cells show S/C phenotype. Since Ia-like antigen was expressed on the neoplastic T cells, it is stressed that antigen-presenting and contrasuppressor cells should also be included in the cell populations which have a possibility to be a normal counterpart of IBL-T.
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8/19. Alterations of blood group antigens in angio-immunoblastic lymphadenopathy with dysproteinemia.

    Antigen analysis of the red cell membrane in a patient with angio-immunoblastic lymphadenopathy with dysproteinemia (AILD) with red cell autoantibody revealed that four blood group antigens had been acquired. These four antigens consisted of S of MNSs blood group, Lua of Lutheran blood group, and K and Kpa of Kell-Cellano blood group. These antigens disappeared and the Coombs' test became negative after complete remission induced by combination chemotherapy. Free amino acid analysis after Dispase treatment of red cell membrane suggested that the antigenic modifications were associated with abnormal composition of amino acids.
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9/19. A case report of the immunodysplasia syndrome and heavy chain disease associated with subacute bacterial endocarditis.

    A 36-year-old man was admitted to Saitama Medical School Hospital, because of a remittent fever which had continued for approximately 6 months, hepatosplenomegaly and lymphadenopathy. He had direct Coombs' test positive auto-immune hemolytic anemia associted with subacute bacterial endocarditis (SBE). The lymphnode demonstrated focal diffuse proliferation of immunoblasts and arborizing vessels with a few small germinal centers, which resembled histological features of the immunoblastic lymphadenopathy. The immunochemical analysis revealed the presence of free IgG Fc fragments in serum. From the above results the patient was diagnosed as immunodysplasia syndrome (IDS) and heavy chain disease (HCD) associated with SBE. It was suggested that the chronic antigenic stimulation due to SBE might have some role in the mechanism of the development of the IDS and HCD in our patient.
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10/19. rubella virus antigen in lymphocytes of patients with angioimmunoblastic lymphadenopathy (AIL).

    Lymph node sections from 14 patients with angioimmunoblastic lymphadenopathy (AIL) were incubated with fluorescein-labeled specific antiserum against rubella virus antigen. In lymphoid cells from 11 patients intracytoplasmic rubella antigen was demonstrated. The results support the idea of a persistent virus infection in AIL.
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